Dr Bird

Question 1

How do most tumours develop?

Answer 1

Develop in epithelium, then metastasise into the mesenchyme and then into the muscle

Question 2

What are the properties of benign tumours?

Answer 2

• Develop in any tissue
  
  • Grow locally
  • May cause problems by pressure on brain or colon obstruction
    - Histologically resemble the tissue of origin
    - Do not spread to distant sites

Question 3

What are the properties of in situ tumours?

Answer 3

• Usually develop in the epithelium
  
  • Have altered histological appearance
  • Variations in cell size and shape
    - Do not invade basement membrane and supporting mesenchyme

Question 4

What are the properties of cancers?

Answer 4

• Fully developed malignant tumours with the specific capacity to invade and destroy the underlying mesenchyme
  - Metastasise
  - Stimulate angiogenesis and development of blood supply

Question 5

What does the ability to metastasise mean?

Answer 5

Can spread to other tissues

Question 6

What are the exogenous agents that can cause mutations in DNA?

Answer 6

• Ionising radiation
  
  • UV radiation
  • Chemical carcinogens
  • Viruses

Question 7

What are the endogenous agents that can cause mutations in DNA?

Answer 7

• Errors in DNA replication
  
  • Intrinsic instability
  • Attack by free radicals

Question 8

What is a transient mutation?

Answer 8

A mutation in DNA that can be repaired

Question 9

How do tumours arise from mutations in DNA?

Answer 9

Permanent mutation occurs and cell division causes a tumour

Question 10

What are the two broad classes of genes involved in the onset of cancer?

Answer 10

Proto-oncogenes and tumour suppressor genes

Question 11

How are proto-oncogenes involved in the onset of cancer?

Answer 11

Excessively active in growth promotion

Question 12

How are tumour suppressor genes?

Answer 12

Normally restrain cell growth but damage to these genes allows inappropriate growth

Question 13

What is the effect of a point mutation?

Answer 13

Amino acid substitution

Question 14

What is the effect of a frameshift mutation?

Answer 14

Scrambled sequence and truncated protein

Question 15

What is the effect of a inappropriate expression or amplification mutation?

Answer 15

Normal protein at the wrong time or too much produced

Question 16

What is the effect of a loss of gene mutation?

Answer 16

Loss of protein

Question 17

What is the effect of a fusion with another gene mutation?

Answer 17

Chimeric protein with altered funtion

Question 18

What is the effect of a epigenetic modification mutation?

Answer 18

Gene silencing and no protein

Question 19

What is the effect of breakage of bonds between purine and deoxyribose?

Answer 19

Random base insertions

Question 20

What is the effect of deamination of cytosine to uridine?

Answer 20

C -> U

Question 21

What is the effect of deamination of methylcytosine to thymidine?

Answer 21

C -> T

Question 22

What is the effect of ionising radiation on DNA?

Answer 22

Single and double stranded DNA breaks and damage from free radicals

Question 23

What is the effect of UV radiation on DNA?

Answer 23

Thymidine dimers

Question 24

What is the function of the p53 gene?

Answer 24

Surveys DNA for damage and elicits a repair

Question 25

How is DNA damage caused by thymidine dimers repaired?

Answer 25

Removal of whole stretch of DNA and resynthesis using opposite strand as template

Question 26

How is DNA damage caused by O-6 methyl guanine repaired?

Answer 26

Directly removed without breaking phosphate backbone

Question 27

How is DNA damage caused by single strand breaks repaired?

Answer 27

Directly repaired

Question 28

How is DNA damage caused by double strand breaks repaired?

Answer 28

Not easily repairable

Question 29

What are the necessary properties for a tumour to spread?

Answer 29

- Self-sufficiency in growth signals - Insensitivity to antigrowth signals - Evasion of apoptosis - Limitless replicative potential - Tissue invasion and metastasis - Sustained angiogenesis

Question 30

What are growth signals generated by?

Answer 30

- Diffusible growth factors - Extracellular matrix components - Cell to cell adhesion molecules

Question 31

What are examples of diffusible growth factors?

Answer 31

- EGF (Epidermal growth factor) - FGF (Fibroblast growth factor) - TGFa (Transforming growth factor alpha) - PDGF (Platelet-derived growth factor)

Question 32

What are the three ways in which cancer cells become growth signal autonomous?

Answer 32

- Modulation of growth factor provision - Modulation of growth factor receptor activity - Modulation of intracellular signalling pathways

Question 33

What is the method of growth factor signalling?

Answer 33

- Growth factor binds to the receptor - Receptor becomes active as a tyrosine kinase and autophosphorylates on tyrosine residues - Some proteins can then dock with the receptor and become activated, others act as substrates for the receptor kinase and become phosphorylated (Usually protein kinases) - Phosphorylated protein then activates a transcription factor

Question 34

How does modulation of growth factor receptor activity cause cancer cells self sufficiency in growth signals?

Answer 34

Overexpression of the growth factor allows tumours to respond to low levels of growth factor that would not normally produce a growth response